Murine Cytomegalovirus Infection Induces Susceptibility to EAE in Resistant BALB/c Mice.Milovanovic J, Popovic B, Milovanovic M, Kvestak D, Arsenijevic A, Stojanovic B, Tanaskovic I, Krmpotic A, Arsenijevic N, Jonjic S, Lukic ML.Front Immunol. 2017;8:192. doi: 10.3389/fimmu.2017.00192.
In contrast to C57BL/6 mice, BALB/c mice are relatively resistant to the induction of experimental autoimmune encephalomyelitis (EAE) after challenge with MOG35-55 peptide. Here, we provide the first evidence that infection with murine cytomegalovirus (MCMV) in adulthood abrogates this resistance. Infected BALB/c mice developed clinical and histological signs similar to those seen in susceptible C57BL/6 mice. In addition to CD4+ cells, large proportion of cells in the infiltrate of diseased BALB/c mice was CD8+, similar with findings in multiple sclerosis. CD8+ cells that responded to ex vivo restimulation with MOG35-55 were not specific for viral epitopes pp89 and m164. MCMV infection favors proinflammatory type of dendritic cells (CD86+CD40+CD11c+) in the peripheral lymph organs, M1 type of microglia in central nervous system, and increases development of Th1/Th17 encephalitogenic cells. This study indicates that MCMV may enhance autoimmune neuropathology and abrogate inherent resistance to EAE in mouse strain by enhancing proinflammatory phenotype of antigen-presenting cells, Th1/Th17, and CD8 response to MOG35-55.
How times change when I first started with EAE, we had the SJL and the PL mouse and BALB/c and notably C57BL/6 were classed as the most genetically resistant mouse strains on the planet.
Amor S, Groome N, Linington C, Morris MM, Dornmair K, Gardinier MV, Matthieu JM, Baker D. Identification of epitopes of myelin oligodendrocyte glycoprotein for the induction of experimental allergic encephalomyelitis in SJL and Biozzi AB/H mice.J Immunol. 1994;153:4349-56.
Then it was shown shortly after that C57BL/6 mice could get MOG induced EAE, using the MOG35-55 that we showed induced disease in ABH (H-2g7= Kd, Ag7, E-, Dq transplantation antigen type that determines which peptides they respond to) mice.
This opened up the use of knockout mice which were typically made on the C57BL/6 (H-2b) or 129 (H-2b) mouse background.
We showed also that the MOG35-55 peptide commonly used may not have been the best peptide in C57BL/6 (H-2Ab) mice
This was repeated a year later, by a group from West Coast USA that forgot not to acknowledge the existence of the early discovery (Bad Science)-I’m not bitter:-)
This is great and bad because C57BL/6 is still a weak susceptibility background and shows gene related differences that disappear as unimportant once you do the same experiment in a high susceptibility strain
Genetic background can result in a marked or minimal effect of gene knockout (GPR55 and CB2 receptor) in experimental autoimmune encephalomyelitis models of multiple sclerosis.
Sisay S, Pryce G, Jackson SJ, Tanner C, Ross RA, Michael GJ, Selwood DL, Giovannoni G, Baker D.PLoS One. 2013 Oct 9;8(10):e76907.
Croxford JL, O’Neill JK, Baker D.Polygenic control of experimental allergic encephalomyelitis in Biozzi ABH and BALB/c mice.J Neuroimmunol. 1997;74(1-2):205-11
Cross AH, McCarron R, McFarlin DE, Raine CS.Adoptively transferred acute and chronic relapsing autoimmune encephalomyelitis in the PL/J mouse and observations on altered pathology by intercurrent virus infection. Lab Invest. 1987; 57:499-512.